The mouse teratogen dinocap has lower A/D ratios and is not teratogenic in the rat and hamster

Abstract

The fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD-1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague-Dawley rat and Syrian golden hamster, and adult-to-developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was administered by gavage to pregnant rats on gestation days 7-20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7-14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental Toxicity: Extrapolation Across Species

“…The experimental designs of these studies were quite inadequate to the stated goal of examining the predictability of A/D ratios across mammalian species because of the selection of submammalian endpoints. Other studies (Rogers, 1987;Rogers et al, 1988) reported that in response to the fungicide dinocap, the mouse had an A/D ratio of -16, whereas the rat and hamster had A/D ratios of 1 .…”

“…It is not surprising that doubts have been expressed concerning the constancy of the A/D ratio calculated across species (Daston and D'Amato, 1989;Daston et al, , 1991Rogers, 1987;Rogers et al, 1988;Schardein, 1987). However, good examples of different ratios for the same chemicals tested in standard evaluations are rare or nonexistent.…”

Developmental and Reproductive Toxicology of Pesticides

“…As cited in CDFA, 1987 As cited in Schardein, 1993 As cited in CDFA, 1987 As cited in Schardein, 1993CDPR Database, 1999Gray et al, 1996Rogers et al, 1988Chernoff et al, 1979bCostlow et al, 1986Rogers et al, 1988 As cited in Schardein, 1993 As cited in Schardein, 1993Vergieva, 1990 As cited in Schardein, 1993 As cited in Schardein, 1993 Goldey andTaylor, 1992 As cited in Schardein, 1993CDPR database, 1999 DPN #413…”